Abstract
While studies of the evolutionary histories of protein families are commonplace, little is known on noncoding RNAs beyond microRNAs and some snoRNAs. Here we investigate in detail the evolutionary history of the nine spliceosomal snRNA families (U1, U2, U4, U5, U6, U11, U12, U4atac, and U6atac) across the completely or partially sequenced genomes of metazoan animals. Representatives of the five major spliceosomal snRNAs were found in all genomes. None of the minor splicesomal snRNAs were detected in nematodes or in the shotgun traces of Oikopleura dioica, while in all other animal genomes at most one of them is missing. Although snRNAs are present in multiple copies in most genomes, distinguishable paralogue groups are not stable over long evolutionary times, although they appear independently in several clades. In general, animal snRNA secondary structures are highly conserved, albeit, in particular, U11 and U12 in insects exhibit dramatic variations. An analysis of genomic context of snRNAs reveals that they behave like mobile elements, exhibiting very little syntenic conservation.
Similar content being viewed by others
References
Bandelt HJ, Dress AWM (1992) A canonical decomposition theory for metrics on a finite set. Adv Math 92:47
Bark C, Weller P, Zabielski J, Pettersson U (1986) Genes for human U4 small nuclear RNA. Gene 50:333–344
Barzotti R, Pelliccia F, Rocchi A (2003) Identification and characterization of U1 small nuclear RNA genes from two crustacean isopod species. Chromosome Res 11:365–373
Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL (2007) GenBank. Nucleic Acids Res 35:D21–D25
Bhathal HS, Zamrod Z, Tobaru T, Stumph WE (1995) Identification of proximal sequence element nucleotides contributing to the differential expression of variant U4 small nuclear RNA genes. J Biol Chem 270:27,629–27,633
Bompfünewerer AF, Flamm C, Fried C, Fritzsch G, Hofacker IL, Lehmann J, Missal K, Mosig A, Müller B, Prohaska SJ, Stadler BMR, Stadler PF, Tanzer A, Washietl S, Witwer C (2005) Evolutionary patterns of non-coding RNAs. Th Biosci 123:301–369
Branlant C, Krol A, Lazar E, Haendler B, Jacob M, GalegoDias L, Pousada C (1983) High evolutionary conservation of the secondary structure and of certain nucleotide sequences of U5 RNA. Nucleic Acids Res 11:8359–8367
Bryant D, Moulton V (2004) Neighbor-net: an agglomerative method for the construction of phylogenetic networks. Mol Biol Evol 21:255–265
Chen L, Lullo DJ, Ma E, Celniker SE, Rio DC, Doudna JA (2005) Identification and analysis of U5 snRNA variants in Drosophila. RNA 11:1473–1477
Collins L, Penny D (2005) Complex spliceosomal organization ancestral to extant eukaryotes. Mol Biol Evol 22:1053–1066
Collins LJ, Macke TJ, Penny D (2004) Searching for ncRNAs in eukaryotic genomes: maximizing biological input with RNA motif. J Integ Bioinf 1:2004–08–04. Available at: http://journalimbiode/indexphp?paperid56
Consortium International Chicken Genome Sequencing (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432:695–716
Cross I, Rebordinos L (2005) 5S rDNA and U2 snRNA are linked in the genome of Crassostrea angulata and Crassostrea gigas oysters: Does the (ct)n(ga)n microsatellite stabilize this novel linkage of large tandem arrays? Genome 48:1116–1119
Dahlberg JE, Lund E (1988) The genes and transcription of the major small nuclear RNAs. In: Birnstiel ML (ed) Structure and function of major and minor small nuclear ribonucleoprotein particles. Springer-Verlag, Berlin, pp 38–70
Denison RA, Van Arsdell SW, Bernstein LB, Weiner AM (1981) Abundant pseudogenes for small nuclear RNAs are dispersed in the human genome. Proc Natl Acad Sci USA 78:810–814
Domitrovich AM, Kunkel GR (2003) Multiple, dispersed human U6 small nuclear RNA genes with varied transcriptional efficiencies. Nucleic Acids Res 31:2344–2352
Drosophila 12 Genomes Consortium (2007) Evolution of genes and genomes on the Drosophila phylogeny. Nature 450:203–218
Ebel C, Frantz C, Paulus F, Imbault P (1999) Trans-splicing and cis-splicing in the colourless euglenoid, Entosiphon sulcatum. Curr Genet 35:542–550
Flicek P, Aken BL, Beal K, Ballester B, Caccamo M, Chen Y, Clarke L, Coates G, Cunningham F, Cutts T, Down T, Dyer SC, Eyre T, Fitzgerald S, Fernandez-Banet J, Gräf S, Haider S, Hammond M, Holland R, Howe KL, Howe K, Johnson N, Jenkinson A, Käahäari A, Keefe D, Kokocinski F, Kulesha E, Lawson D, Longden I, Megy K, Meidl P, Overduin B, Parker A, Pritchard B, Prlic A, Rice S, Rios D, Schuster M, Sealy I, Slater G, Smedley D, Spudich G, Trevanion S, Vilella AJ, Vogel J, White S, Wood M, Birney E, Cox T, Curwen V, Durbin R, Fernandez-Suarez XM, Herrero J, Hubbard TJP, Kasprzyk A, Proctor G, Smith J, Ureta-Vidal A, Searle S (2008) Ensembl 2008. Nucleic Acids Res 36:D707–D714
Forbes DJ, Kirschner MW, Caput D, Dahlberg JE, Lund E (1984) Differential expression of multiple U1 small nuclear RNAs in oocytes and embryos of Xenopus laevisi. Cell 38:681–689
Gautheret D, Lambert A (2001) Direct RNA motif definition and identification from multiple sequence alignments using secondary structure profiles. J Mol Biol 313:1003–1011
Giribet G, Edgecombe GD, Wheeler WC (2001) Arthropod phylogeny based on eight molecular loci and morphology. Nature 413:157–161
Gonzalez IL, Sylvester JE (2001) Human rDNA: evolutionary patterns within the genes and tandem arrays derived from multiple chromosomes. Genomics 73:255–263
Griffiths-Jones S (2005) RALEE—RNA alignment editor in Emacs. Bioinformatics 21:257–259
Griffiths-Jones S, Moxon S, Marshall M, Khanna A, Eddy SR, Bateman A (2005) Rfam: annotating non-coding RNAs in complete genomes. Nucleic Acids Res 33:D121–D124
Hastings KE (2005) SL trans-splicing: Easy come or easy go? Trends Genet 21:240–247
Hausner TP, Giglio LM, Weiner AM (1990) Evidence for basepairing between mammalian U2 and U6 small nuclear ribonucleoprotein particles. Genes Dev 4:2146–2156
Hernandez N (2001) Small nuclear RNA genes: a model system to study fundamental mechanisms of transcription. J Biol Chem 276:26,733–26,736
Hillis DM, Dixon MT (1991) Ribosomal DNA: molecular evolution and phylogenetic inference. Q Rev Biol 66:411–453
Hinas A, Larsson P, Avesson L, Kirsebom LA, Virtanen A, Söderbom F (2006) Identification of the major spliceosomal RNAs in Dictyostelium discoideum reveals developmentally regulated U2 variants and polyadenylated snRNAs. Eukaryot Cell 5:924–934
Hofacker IL, Fontana W, Stadler PF, Bonhoeffer LS, Tacker M, Schuster P (1994) Fast folding and comparison of RNA secondary structures. Monatsh Chem 125:167–188
Hofacker IL, Fekete M, Stadler PF (2002) Secondary structure prediction for aligned RNA sequences. J Mol Biol 319:1059–1066
Hubbard T, Andrews D, Caccamo M, Cameron G, Chen Y, Clamp M, Clarke L, Coates G, Cox T, Cunningham F, Curwen V, Cutts T, Down T, Durbin R, Fernandez-Suarez XM, Gilbert J, Hammond M, Herrero J, Hotz H, Howe K, Iyer V, Jekosch K, Kahari A, Kasprzyk A, Keefe D, Keenan S, Kokocinsci F, London D, Longden I, McVicker G, Melsopp C, Meidl P, Potter S, Proctor G, Rae M, Rios D, Schuster M, Searle S, Severin J, Slater G, Smedley D, Smith J, Spooner W, Stabenau A, Stalker J, Storey R, Trevanion S, Ureta-Vidal A, Vogel J, White S, Woodwark C, Birney E (2005) Ensembl 2005. Nucleic Acids Res 33:D447–D453
Huson DH, Bryant D (2006) Application of phylogenetic networks in evolutionary studies. Mol Biol Evol 23:254–267
Kirsten T, Rahm E (2006) BioFuice: mapping-based data intergation in bioinformatics. In: Leser U, Naumann F, Eckman B (eds) Proceedings of the 3rd International Workshop on Data Integration in the Life Sciences (DILS), vol 4075. Springer Verlag, Berlin, pp 124–135
König H, Matter N, Bader R, Thiele W, Müller F (2007) Splicing segregation: the minor spliceosome acts outside the nucleus and controls cell proliferation. Cell 131:718–729
Korf GM, Stumph WE (1986) Chicken U2 and U1 RNA genes are found in very different genomic environments but have similar promoter structures. Biochemistry 25:2041–2047
Krol A, Branlant C, Lazar E, Gallinaro H, Jacob M (1981) Primary and secondary structures of chicken, rat and man nuclear U4 RNAs. Homologies with U1 and U5 RNAs. Nucleic Acids Res 9:2699–2716
Kunkel GR, Pederson T (1988) Upstream elements required for efficient transcription of a human U6 RNA gene resemble those of U1 and U2 genes even though a different polymerase is used. Genes Dev 2:196–204
Kyriakopoulou C, Larsson P, Liu L, Schuster J, Söderbom F, Kirsebom LA, Virtanen A (2006) U1-like snRNAs lacking complementarity to canonical 5′ splice sites. RNA 12:1603–1611
Liao D (1999) Concerted evolution: molecular mechanism and biological implications. Am J Hum Genet 64:24–30
Liao D, Weiner AM (1995) Concerted evolution of the tandemly repeated genes encoding primate U2 small nuclear RNA (the RNU2 locus) does not prevent rapid diversification of the (CT)n(GA)n microsatellite embedded within the U2 repeat unit. Genomics 30:583–593
Liao D, Pavelitz T, Kidd JR, Kidd KK, Weiner AM (1997) Concerted evolution of the tandemly repeated genes encoding human U2 snRNA (the RNU2 locus) involves rapid intrachromosomal homogenization and rare interchromosomal gene conversion. EMBO J 16:588–598
Lo PC, Mount SM (1990) Drosophila melanogaster genes for U1 snRNA variants and their expression during development. Nucleic Acids Res 18:6971–6979
López MD, Alm Rosenblad M, Samuelsson T (2008) Computational screen for spliceosomal RNA genes aids in defining the phylogenetic distribution of major and minor spliceosomal components. Nucleic Acids Res 36:3001–3010
Lorkovíc ZJ, Lehner R, Forstner C, Barta A (2005) Evolutionary conservation of minor U12-type spliceosome between plants and humans. RNA 11:1095–1107
Macke TJ, Ecker DJ, Gutell RR, Gautheret D, Case DA, Sampath R (2001) RNAMotif, an RNA secondary structure definition and search algorithm. Nucleic Acids Res 29(22):4724–4735
Manchado M, Zuasti E, Cross I, Merlo A, Infante C, Rebordinos L (2006) Molecular characterization and chromosomal mapping of the 5S rRNA gene in Solea senegalensis: a new linkage to the U1, U2, and U5 small nuclear RNA genes. Genome 49:79–86
Mattaj IW, Zeller R (1983) Xenopus laevis U2 snRNA genes: tandemly repeated transcription units sharing 5′ and 3′ flanking homology with other RNA polymerase II transcribed genes. EMBO J 2:1883–1891
Missal K, Rose D, Stadler PF (2005) Non-coding RNAs in Ciona intestinalis. Bioinformatics 21(S2):i77–i78
Missal K, Zhu X, Rose D, Deng W, Skogerbø G, Chen R, Stadler PF (2006) Prediction of structured non-coding RNAs in the genome of the nematode Caenorhabitis elegans. J Exp Zool Mol Dev Evol 306B:379–392
Mitrovich QM, Guthrie C (2007) Evolution of small nuclear RNAs in S cerevisiae, C albicans, and other hemiascomycetous yeasts. RNA 13:2066–2080
Montzka KA, Steitz JA (1988) Additional low-abundance human small nuclear ribonucleoproteins: U11, U12, etc. Proc Natl Acad Sci USA 85:8885–8889
Morales J, Borrero M, Sumerel J (1997) Identification of developmentally regulated sea urchin U5 snRNA genes. DNA Seq 7:243–259
Mount SM, Steitz JA (1981) Sequence of U1 RNA from Drosophila melanogaster: implications for U1 secondary structure and possible involvement in splicing. Nucleic Acids Res 9:6351–6368
Mount SM, Gotea V, Lin CF, Hernandez K, Makałowski W (2007) Spliceosomal small nuclear RNA genes in 11 insect genomes. RNA 13:5–14
Myslinksi E, Krol A, Carbon P (2004) Characterization of snRNA and snRNA-type genes in the pufferfish Fugu rubripes. Gene 330:149–158
Myslinski E, Branlant C, Wieben ED, Pederson T (1984) The small nuclear RNAs of Drosophila. J Mol Biol 180:927–945
Nei M, Rooney AP (2005) Concerted and birth-and-death evolution of multigene families. Annu Rev Genet 39:121–152
Nilsen TW (2003) The spliceosome: The most complex macromolecular machine in the cell? Bioessays 25:1147–1149
Otake LR, Scamborova P, Hashimoto C, Steitz JA (2002) The divergent U12-type spliceosome is required for pre-mRNA splicing and is essential for development in Drosophila. Mol Cell 9:439–446
Papillon D, Perez Y, Caubit X, Le Parco Y (2006) Systematics of chaetognatha under the light of molecular data, using duplicated ribosomal 18S DNA sequences. Mol Phylogenet Evol 38:621–634
Patel AA, Steitz JA (2003) Splicing double: insights from the second spliceosome. Nat Rev Mol Cell Biol 4:960–970
Pavelitz T, Liao D, Weiner AM (1999) Concerted evolution of the tandem array encoding primate U2 snRNA (the RNU2 locus) is accompanied by dramatic remodeling of the junctions with flanking chromosomal sequences. EMBO J 18:3783–3792
Pelliccia F, Barzotti R, Bucciarelli E, Rocchi A (2001) 5S ribosomal and U1 small nuclear RNA genes: a new linkage type in the genome of a crustacean that has three different tandemly repeated units containing 5S ribosomal DNA sequences. Genome 44:331–335
Pereira-Simon S, Sierra-Montes JM, Ayesh K, Martinez L, Socorro A, Herrera RJ (2004) Variants of U1 small nuclear RNA assemble into spliceosomal complexes. Insect Mol Biol 13:189–194
Putnam NH, Butts T, Ferrier DEK, Furlong RF, Hellsten UK, Takeshi Robinson-Rechavi M, Shoguchi E, Terry A, Yu JK, Benito-Gutíerrez E, Dubchak I, Garcia-Fernàndez J, Gibson-Brown JJ, Grigoriev IV, Horton AC, de Jong PJ, Jurka J, Kapitonov VV, Kohara Y, Kuroki Y, Lindquist E, Lucas S, Osoegawa K, Pennacchio LA, Salamov AA, Satou Y, Sauka-Spengler T, Schmutz J, Shin-I T, Toyoda A, Bronner-Fraser M, Fujiyama A, Holland LZ, Holland PWH, Satoh N, Rokhsar DS (2008) The amphioxus genome and the evolution of the chordate karyotype. Nature 453:1064–1071
Russell AG, Charette JM, Spencer DF, Gray MW (2006a) An early evolutionary origin for the minor spliceosome. Nature 443:863–866
Russell AG, Charette JM, Spencer DF, Gray MW (2006b) An early evolutionary origin for the minor spliceosome. Nature 443:863–866
Schlötterer C, Tautz D (1994) Chromosomal homogeneity of Drosophila ribosomal DNA arrays suggests intrachromosomal exchanges drive concerted evolution. Curr Biol 4:777–783
Schmitz J, Zemann A, Churakov G, Kuhl H, Grützner F, Reinhardt R, Brosius J (2008) Retroposed SNOfall—a mammalianwide comparison of platypus snornas. Genome Res 18:1005–1010
Schneider C, Will CL, Brosius J, Frilander M, Lührmann R (2004) Identification of an evolutionarily divergent U11 small nuclear ribonucleoprotein paricle in Drosophila. Proc Natl Acad Sci USA 101(26):9584–9589
Shambaugh JD, Hannon GE, Nilsen TW (1994) The spliceosomal U small nuclear RNAs of Ascaris lumbricoides. Mol Biochem Parasitol 64:349–352
Sheth N, Roca X, Hastings ML, Roeder T, Krainer AR, Sachidanandam R (2006) Comprehensive splice-site analysis using comparative genomics. Nucleic Acids Res 34:3955–3967
Shukla GC, Padgett RA (1999) Conservation of functional features of U6atac and U12 snRNAs between vertebrates and higher plants. RNA 5:525–538
Shukla GC, Padgett RA (2004) U4 small nuclear RNA can function in both the major and minor spliceosomes. Proc Natl Acad Sci USA 101:93–98
Shukla GC, Cole AJ, Dietrich RC, Padgett RA (2002) Domains of human U4atac snRNA required for U12-dependent splicing in vivo. Nucleic Acids Res 30:4650–4657
Sierra-Montes JM, Freund AV, Ruiz LM, Szmulewicz MN, Rowold DJ, Herrera RJ (2002) Multiple forms of U2 snRNA coexist in the silk moth Bombyx mori. Insect Mol Biol 11:105–114
Sierra-Montes JM, Pereira-Simon S, Freund AV, Ruiz LM, Szmulewicz MN, Herrera RJ (2003) A diversity of U1 small nuclear RNAs in the silk moth Bombyx mori. Insect Biochem Mol Biol 33:29–39
Sierra-Montes JM, Pereira-Simon S, Smail SS, Herrera RJ (2005) The silk moth Bombyx mori U1 and U2 snRNA variants are differentially expressed. Gene 352:127–136
Smail SS, Ayesh K, Sierra-Montes JM, Herrera RJ (2006) U6 snRNA variants isolated from the posterior silk gland of the silk moth Bombyx mori. Insect Biochem Mol Biol 36:454–465
Sontheimer EJ, Steitz JA (1992) Three novel functional variants of human U5 small nuclear RNA. Mol Cell Biol 12:734–746
Stefanovic B, Marzluff WF (1992) Characterization of two developmentally regulated sea urchin U2 small nuclear RNA promoters: a common required TATA sequence and independent proximal and distal elements. Mol Cell Biol 12:650–660
Stefanovic B, Li JM, Sakallah S, Marzluff WF (1991) Isolation and characterization of developmentally regulated sea urchin U2 snRNA genes. Dev Biol 148:284–294
Tarn WY, Yario TA, Steitz JA (1995) U12 snRNAs in vertebrates: evolutionary conservation of 5′ sequences implicated in splicing of pre-mRNAs containing a minor class of introns. RNA 1:644–656
Telford MJ, Holland PWH (1997) Evolution of 28S ribosomal DNA in chaetognaths: duplicate genes and molecular phylogeny. J Mol Evol 44:135–144
The Chimpanzee Sequencing Analysis Consortium (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437:69–87
Thomas J, Lea K, Zucker-Aprison E, Blumenthal T (1990) The spliceosomal snRNAs of Caenorhabditis elegans. Nucleic Acids Res 18:2633–2642
Tichelaar JW, Wieben ED, Reddy R, Vrabel A, Camacho P (1998) In vivo expression of a variant human U6 RNA from a unique, internal promoter. Biochemistry 37:12, 943–12,951
Valadkhan S (2005) snRNAs as the catalysts of pre-mRNA splicing. Curr Opin Chem Biol 9:603–608
Valadkhan S (2007) The spliceosome: caught in a web of shifting interactions. Curr Opin Struct Biol 17:310–315
Valadkhan S, Mohammadi A, Wachtel C, Manley JL (2007) Protein-free spliceosomal snRNAs catalyze a reaction that resembles the first step of splicing. RNA 13:2300–2311
Weber MJ (2006) Mammalian small nucleolar RNAs are mobile genetic elements. PLoS Genet 2:e205
Will CL, Lührmann R (2005) Splicing of a rare class of introns by the U12-dependent spliceosome. Biol Chem 386:713–724
Acknowledgments
This work was supported in part by the Graduierten-Kolleg Wissensrepräsentation and by the Bioinformatics Initiative of the Deutsche Forschungs-Gemeinschaft (DFG). Special thanks go to Petra Pregel and Jens Steuck for making the work much easier.
Author information
Authors and Affiliations
Corresponding author
Electronic Supplementary Material
Rights and permissions
About this article
Cite this article
Marz, M., Kirsten, T. & Stadler, P.F. Evolution of Spliceosomal snRNA Genes in Metazoan Animals. J Mol Evol 67, 594–607 (2008). https://doi.org/10.1007/s00239-008-9149-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00239-008-9149-6